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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2000-8-18
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pubmed:abstractText |
In a search for new inhibitors of the IFN-gamma mediated signal transduction in HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, the novel pyran-dione trichodion was isolated from fermentations of the imperfect fungus Trichosporiella sp. 20-95. The compound inhibits the IFN-gamma mediated expression of the reporter gene with IC(50) values of 21-42 microM (5-10 microgram/ml). The NF-kappaB and AP-1 mediated expression of the reporter gene are inhibited with IC(50) values of 42-84 microM (10-20 microgram/ml) and 21 microM (5 microgram/ml) respectively. Western blotting with COX-2 and NOS II antibodies showed that the expression of both proinflammatory enzymes is almost completely inhibited at 21-42 microM (5-10 microgram/ml) in LPS/IFN-gamma stimulated J774 mouse macrophages. Studies on the mode of action of the compound revealed that the inhibition of the NF-kappaB dependent pathway is due to the stabilization of the IkappaB protein and the inhibition of the IFN-gamma dependent signaling is caused by an inhibition of the phosphorylation of the STAT1alpha transcription factor.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0014-5793
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
477
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
219-23
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10908724-Animals,
pubmed-meshheading:10908724-Base Sequence,
pubmed-meshheading:10908724-Cyclooxygenase 2,
pubmed-meshheading:10908724-DNA Primers,
pubmed-meshheading:10908724-HeLa Cells,
pubmed-meshheading:10908724-Humans,
pubmed-meshheading:10908724-Isoenzymes,
pubmed-meshheading:10908724-Macrophages,
pubmed-meshheading:10908724-Membrane Proteins,
pubmed-meshheading:10908724-Mice,
pubmed-meshheading:10908724-Mitosporic Fungi,
pubmed-meshheading:10908724-Nitric Oxide Synthase,
pubmed-meshheading:10908724-Phosphorylation,
pubmed-meshheading:10908724-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10908724-Protein Kinases,
pubmed-meshheading:10908724-Pyrones,
pubmed-meshheading:10908724-Signal Transduction
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pubmed:year |
2000
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pubmed:articleTitle |
Trichodion, a new inhibitor of inflammatory signal transduction pathways from a Trichosporiella species.
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pubmed:affiliation |
Institut für Biotechnologie und Wirkstoff-Forschung e.V., Erwin-Schrödinger-Str. 56, D-67663, Kaiserslautern, Germany. erkel@ibwf.uni-kl.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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